In vivo adenosine receptor preconditioning reduces myocardial infarct size via subcellular ERK signaling

Reid, Easton A.; Kristo, Gentian; Yoshimura, Yukihiro; Ballard-Croft, Cherry; Keith, Byron J.; Mentzer, Robert M.; Lasley, Robert D.

doi:10.1152/ajpheart.01009.2004

Cited by 48 publications

(55 citation statements)

References 35 publications

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Section: Discussionmentioning

confidence: 81%

“…Stimulation of both adenosine A 1 and A 2a receptors is associated with the activation of multiple protein kinases that have been implicated in cardioprotection (11,29,36). In a previous study (29), we reported that ZM-241385 appeared to blunt AMP579-mediated increases in the phosphorylation of the myocardial mitogenactivated protein kinase, extracellular signal-regulated kinase, before ischemia. Our observations that the A 2a agonist alone did not induce cardioprotection, but the antagonist ZM-241385 blocked protection induced by A 1 activation, suggest that occupation of the A 2a and/or A 2b receptor, either by the A 1 agonist or by increases in endogenous adenosine during ischemia or reperfusion, is necessary for adenosine A 1 receptormediated cardioprotection.…”

Section: Discussionmentioning

confidence: 81%

“…Abe et al (1) reported that in vivo neural stunning of sympathetic activation in canine coronary circulation was due to the combined effects of A 1 and A 2a receptor activation. We have previously reported (29) that the cardioprotective effect of the adenosine receptor agonist AMP579, which has a high affinity for both A 1 and A 2a receptors (31), was blocked by both the A 1 antagonist DPCPX and the A 2a antagonist ZM-241385. Reperfusion cardioprotection (i.e., postconditioning) with AMP579 in rabbit myocardium is mediated via A 2a receptor activation, based on blockade by the A 2a antagonist ZM-241385; however, the selective A 2a agonist CGS-21680 was unable to mimic these effects (11,35).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that cardiac adenosine A 2a receptors modulate the adenosine A 1 receptor anti-adrenergic effect (22, 34). There is also evidence implicating adenosine receptor subtype interactions in the beneficial effects of adenosine in ischemic-reperfused myocardium (11,19,26,29,30). Given the increasing evidence for adenosine receptor interactions in various tissues, including the heart, we tested the effects of A 1 , A 2a , and A 3 receptor antagonists on the cardioprotective effects of adenosine receptor agonist pretreatment in an in vivo rat model of regional myocardial ischemia.…”

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confidence: 99%

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The A_2a/A_2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium

Lasley¹,

Kristo²,

Keith³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Lasley RD, Kristo G, Keith BJ, Mentzer RM, Jr. The A2a/A2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium. Am J Physiol Heart Circ Physiol 292: H426 -H431, 2007. First published September 15, 2006; doi:10.1152/ajpheart.00675.2006.-There is increasing evidence for interactions among adenosine receptor subtypes in the brain and heart. The purpose of this study was to determine whether the adenosine A 2a receptor modulates the infarct size-reducing effect of preischemic administration of adenosine receptor agonists in intact rat myocardium. Adult male rats were submitted to in vivo regional myocardial ischemia (25 min) and 2 h reperfusion. Vehicle-treated rats were compared with rats pretreated with the A 1 agonist 2-chloro-N 6 -cyclopentyladenosine (CCPA, 10 g/kg), the nonselective agonist 5Ј-N-ethylcarboxamidoadenosine (NECA, 10 g/kg), or the A 2a agonist 2-[4-(2-carboxyethyl)phenethylamino]-5Ј-N-methylcarboxamidoadenosine (CGS-21680, 20 g/kg). Additional CCPA-and NECA-treated rats were pretreated with the A 1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 g/kg), the A 2a/ A 2b antagonist 4-(-2-[7-amino-2-{2-furyl}{1,2,4}triazolo{2,3-a} {1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM-241385, 1.5 mg/kg) or the A 3 antagonist 3-propyl-6-ethyl-5[(ethylthio)carbonyl]-2-phenyl-4-propyl-3-pyridine carboxylate (MRS-1523, 2 mg/kg). CCPA and NECA reduced myocardial infarct size by 50% and 35%, respectively, versus vehicle, but CGS-21680 had no effect. DPCPX blunted the bradycardia associated with CCPA and NECA, whereas ZM-241385 attenuated their hypotensive effects. Both DPCPX and ZM-241385 blocked the protective effects of CCPA and NECA. The A 3 antagonist did not alter the hemodynamic effects of CCPA or NECA, nor did it alter adenosine agonist cardioprotection. None of the antagonists alone altered myocardial infarct size. These findings suggest that although preischemic administration of an A2a receptor agonist does not induce cardioprotection, antagonism of the A2a and/or the A2b receptor blocks the cardioprotection associated with adenosine agonist pretreatment. adenosine receptor; ischemia-reperfusion; infarct reduction IT IS NOW WELL-RECOGNIZED that the administration of adenosine before myocardial ischemia (i.e., pretreatment) protects against both reversible and irreversible injury, an effect that appears to be mediated via the activation of cardiomyocyte A 1 and/or A 3 adenosine receptor subtypes (14, 21). The results of a very limited number of reports indicate that the administration of adenosine A 2a agonists before ischemia is not cardioprotective (1,13,32,33). However, there is now significant evidence that A 2a receptor activation during reperfusion (i.e., postconditioning) reduces myocardial infarct size (7,11,12,(35)(36)(37). The results of in vivo studies suggest that A 2a receptor postconditioning is mediated primarily via inhibition of inflammatory cell adhesion to vascular endothelial cells (7, 37). Additional reports...

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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The A_2a/A_2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium

Lasley¹,

Kristo²,

Keith³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…Coupling to K + channels in supraventricular tissue is responsible for the bradycardiac effect of adenosine on heart function 12 . In the heart, A 1 AR and A 2A AR agonistinduced preconditioning has been suggested to occur via modulation of p44/42 extracellular signal-regulated protein kinase (ERK) signalling 13 .…”

Section: Ar Signalling Pathways and Regulationmentioning

confidence: 99%

Adenosine receptors as therapeutic targets

Jacobson

Gao

2006

Nat Rev Drug Discov

1,253

1,361

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Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide range of conditions, including cerebral and cardiac ischaemic diseases, sleep disorders, immune and inflammatory disorders and cancer. After more than three decades of medicinal chemistry research, a considerable number of selective agonists and antagonists of adenosine receptors have been discovered, and some have been clinically evaluated, although none has yet received regulatory approval. However, recent advances in the understanding of the roles of the various adenosine receptor subtypes, and in the development of selective and potent ligands, as discussed in this review, have brought the goal of therapeutic application of adenosine receptor modulators considerably closer.

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The role of post‐translational modifications in acute and chronic cardiovascular disease

Smith

White

2014

Proteomics Clinical Apps

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Cardiovascular disease (CVD) in one of the leading causes of mortality and morbidity worldwide, accounting for both primary diseases of the heart and vasculature and arising as a co-morbidity with numerous pathologies, including type 2 diabetes mellitus (T2DM). There has been significant emphasis on the role of the genome in CVD, aiding in the definition of 'at-risk' patients. The extent of disease penetrance however, can be influenced by environmental factors that are not detectable by investigating the genome alone. By targeting the transcriptome in response to CVD, the interplay between genome and environment is more apparent, however this implies the level of protein expression without reference to proteolytic turnover, or potentially more importantly, without defining the role of PTMs in the development of disease. Here, we discuss the role of both brief and irreversible PTMs in the setting of myocardial ischemia/reperfusion injury. Key proteins involved in calcium regulation have been observed as differentially modified by phosphorylation/O-GlcNAcylation or phosphorylation/redox modifications, with the level of interplay dependent on the physiological or pathophysiological state. The ability to modify crucial sites to produce the desired functional output is modulated by the presence of other PTMs as exemplified in the T2DM heart, where hyperglycemia results in aberrant O-GlcNAcylation and advanced glycation end products. By using the signalling events predicted to be critical to post-conditioning, an intervention with great promise for the cardioprotection of the ischemia/reperfusion injured heart, as an example, we discuss the level of PTMs and their interplay. The inability of post-conditioning to protect the diabetic heart may be regulated by aberrant PTMs influencing those sites necessary for protection.

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In vivo adenosine receptor preconditioning reduces myocardial infarct size via subcellular ERK signaling

Cited by 48 publications

References 35 publications

The A_2a/A_2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium

The A_2a/A_2b receptor antagonist ZM-241385 blocks the cardioprotective effect of adenosine agonist pretreatment in in vivo rat myocardium

Adenosine receptors as therapeutic targets

The role of post‐translational modifications in acute and chronic cardiovascular disease

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